The long term goals of the project are to define the physiology and biochemistry of fat digestion. The specific aims of the proposal are: (1) define the role of pancreatic lipase related protein 2 (PLRP2), a homologue of pancreatic triglyceride lipase, in fat digestion at various ages by characterizing fat utilization in PLRP2 deficient mice. The approach to this aim will be to determine fecal fat excretion in PLRP2 deficient mice at various stages of development and after being fed different levels of fat. (2) delineate the role of colipase in dietary fat digestion by ablating the gene encoding procolipase in mice. These mice will be created and the absence of colipase expression determined by mRNA and protein analysis. Fat absorption will be ascertained in the deficient mice; (3) demonstrate that enterostatin, the activation peptide of procolipase, mediates satiety and controls obesity by creating enterostatin deficient mice with gene ablation and transgenic techniques; and (4) characterize the receptor for enterostatin on neuronal and nonneuronal cells by measuring binding of radiolabeled enterostatin. Detailed knowledge of the receptor properties may reveal a novel approach to obesity treatment and fat satiety.